Document Detail

Cardiac morphogenesis: matrix metalloproteinase coordination of cellular mechanisms underlying heart tube formation and directionality of looping.
MedLine Citation:
PMID:  15844197     Owner:  NLM     Status:  MEDLINE    
During heart organogenesis, the spatiotemporal organization of the extracellular matrix (ECM) undergoes significant remodeling. Because matrix metalloproteinases (MMPs) are known to be key regulators of cell-matrix interactions, we analyzed the role(s) of MMPs, and specifically MMP-2, in early heart development. Both MMP-2 neutralizing antibody and the broad-spectrum MMP inhibitor Ilomastat in a temporal manner, when applied between chick embryonic stages 5 (primitive streak stage) to stage 12 ( approximately 16-somites), produced severe heart tube defects. Exposure to the MMP inhibitor at stage 5 produced various degrees of cardia bifida. At the seven-somite stage, MMP-2/Ilomastat inhibition caused a shift in normal left-right patterning of cell proliferation within the dorsal mesocardium and mesoderm of the anterior heart field that correlated with a change in looping direction. MMP inhibition at the 10- to 12-somite stage resulted in an arrest of heart tube bending by inhibiting the breakdown of the dorsal mesocardial ECM. The experimental observations suggest that MMP activity regulates the coordination of early heart organogenesis by affecting ventral closure of the heart and gut tubes, asymmetric cell proliferation in the dorsal mesocardium to drive looping direction, and ECM degradation within the dorsal mesocardium allowing looping to proceed toward completion.
Kersti K Linask; Mingda Han; Dong Hong Cai; Philip R Brauer; Shyam M Maisastry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Developmental dynamics : an official publication of the American Association of Anatomists     Volume:  233     ISSN:  1058-8388     ISO Abbreviation:  Dev. Dyn.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-21     Completed Date:  2005-10-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9201927     Medline TA:  Dev Dyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  739-53     Citation Subset:  IM    
University of South Florida, Department of Pediatrics, The Children's Research Institute, St. Petersburg, Florida 33701, USA.
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MeSH Terms
Body Patterning
Cell Movement
Cell Proliferation
Chick Embryo
Epithelial Cells / cytology
Extracellular Matrix / metabolism
Heart / embryology*
Matrix Metalloproteinase 2 / antagonists & inhibitors,  metabolism*
Myocardium / cytology,  enzymology*
Protease Inhibitors / pharmacology
Time Factors
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Reg. No./Substance:
0/Protease Inhibitors; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC Metalloproteinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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